The current proposal is a competitive renewal of a K24 Midcareer Investigator Award in Patient- oriented research for Mark S. Sulkowski, MD of the Johns Hopkins University School of Medicine. Dr. Sulkowski is an infectious disease-trained clinical investigator at Johns Hopkins University where he is a Professor of Medicine and directs a highly productive clinical research program focused on the intersection of HIV, hepatitis C virus (HCV), and substance use. His research is supported by an NIH R01 and the NIH-funded AIDS Clinical Trials Group (ACTG); he serves as the Chair of the ACTG Hepatitis Transformative Sciences Group. During his time at Johns Hopkins, he has made substantial scientific contributions to the development of revolutionary HCV treatments. His work has also significantly advanced the clinical management of HCV disease in persons living with HIV infection. Current HCV therapies can cure more than 95% of individuals who are successfully linked to care and initiate treatment including individuals with HIV coinfection and those who use drugs. However, in 2013, the annual HCV-related mortality surpassed the combined number of deaths from 60 other infections reported to the Centers for Disease Control, including HIV. While HCV-related deaths are most common in older adults with long-standing HCV, the United States has also witnessed the resurgence of new HCV infections in young adults as the result of the injection opiate epidemic. In 2017, the National Academy of Medicine concluded that treating all persons with chronic HCV would reduce new infections by 90% and HCV-related deaths by 65% by 2030. To achieve this ambitious goal, strategies to prevent and cure HCV in persons who inject drugs are urgently needed. Renewal of this K24 is critical to Dr. Sulkowski's plan to investigate such strategies. Project aims include new collaborative research to evaluate the role of injection networks in HCV treatment and prevention and to assess the feasibility of HCV clinic-based buprenorphine-naloxone to increase concurrent treatment of HCV and opiate use disorders. For progress to be made toward achieving the Academy's goals, young clinical investigators are also needed. During the initial K24 period, Dr. Sulkowski had over 67 publications; the majority of which included young investigators who are pursuing careers in academic research. Renewal of this K24 award is critical to his desire to continue to mentor junior researchers in the key fields of HIV and HCV and to continue to evolve his research through new training in substance abuse research. The protected time afforded by this award is essential to Dr. Sulkowski achieving these goals.